Gypenoside XVII alleviates early diabetic retinopathy by regulating Muller cell apoptosis and autophagy in db/db mice
Gypenoside XVII alleviates early diabetic retinopathy by regulating Muller cell apoptosis and autophagy in db/db mice
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绞股蓝皂苷 XVII 通过调节 db/db 小鼠的 Müller 细胞凋亡和自噬减轻早期糖尿病视网膜病变
DOI：
10.1016/j.ejphar.2021.173893
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发表时间：
2021-01-27
影响因子：
5
通讯作者：
Sun, Xiaobo
中科院分区：
文献类型：
--
作者：
Luo, Yun;Dong, Xi;Sun, Xiaobo
糖尿病视网膜病变（diabetic retinopathy，DR）是一种常见的危害视力的疾病。Muller细胞是重要的胶质细胞，参与血视网膜屏障并促进视网膜生理和结构稳态的维持。Muller细胞凋亡和自噬在DR的发病机制中起重要作用，绞股蓝皂苷XVII（Gyp-17）具有较强的抗凋亡和自噬活性。然而，Gyp-17对DR的作用及其作用机制尚未阐明。本研究探讨了Gyp-17对db/db小鼠早期DR和Muller细胞损伤的影响。测定血糖和血脂。应用光学相干断层扫描和荧光素眼底血管造影分别检测视网膜厚度和血管渗漏。苏木精-伊红染色观察视网膜的病理变化。视网膜氧化环境和细胞凋亡和自噬监测使用商业试剂盒，免疫荧光，和Western印迹分析。结果显示，与模型组相比，Gyp-17对血糖和血脂水平无明显影响，但维持正常的视网膜通透性、生理结构、高抗氧化酶表达和内核层厚度。Western blot和TUNEL检测结果显示，Gyp-17组与模型组相比，促凋亡相关蛋白的表达明显降低，促自噬相关蛋白的表达明显增加。免疫荧光共定位显示Gyp-17的调节作用可能集中在Muller细胞。这些数据有力地证明Gyp-17通过减少Muller细胞中的凋亡和增加自噬来预防早期DR。Gyp-17可能是早期DR治疗的候选药物。
Diabetic retinopathy (DR) is a widespread vision-threatening disease in working people. Muller cells are important glial cells that participate in the blood retinal barrier and promote the maintenance of retinal physiological and structural homeostasis. Muller cell apoptosis and autophagy play an important role in the pathogenesis of DR. Gypenoside XVII (Gyp-17) exerts strong antiapoptotic and autophagic activities. However, the effect of Gyp-17 on DR and its mechanism of action have not been elucidated. This study explored the effect of Gyp-17 on early DR and Muller cell injury in db/db mice. Blood glucose and blood lipids were measured. Optical coherence tomography and fundus fluorescein angiography were applied to detect retinal thickness and vascular leakage, respectively. Hematoxylin eosin staining assessed the pathological changes of the retina. Retinal oxidative environment and cell apoptosis and autophagy were monitored using commercial kits, immunofluorescence, and Western blot assays. Results showed that Gyp-17 exerted no significant effect on blood glucose and lipid levels but maintained normal retinal permeability, physiological structure, high anti-oxidative enzyme expression, and the thickness of the inner nuclear layer compared with the model group. Moreover, Western blot analysis and TUNEL assay indicated that Gyp-17 significantly decreased pro-apoptotic-related protein expression and increased pro-autophagy-related protein expression compared with the model group. Immunofluorescence colocalization exhibited that the regulating action of Gyp-17 may focus on Muller cells. These data strongly demonstrate that Gyp-17 prevents early DR by decreasing apoptosis and increasing autophagy in Muller cells. Gyp-17 may be a candidate drug for early DR therapy.